Lack of Modifying Effects of 2,6-Dimethylaniline on Lung Carcinogenesis in Transgenic Mice Carrying Human Prototype c-Ha-<i>ras</i> Gene Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

Abstract

2,6-Dimethylaniline (DMA) is known as a major metabolite of xylazine, α2-adrenergic agonist used as a tranquilizer for domestic animals, and has been reported to have a carcinogenic potential to the nasal cavity in rats as well as a nasal tumor pomoting effect in rats. In order to examine whether DMA has any tumor modifying effect in the other respiratory organs, transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) that are highly susceptible to genotoxic carcinogens were given diet containing 0 or 3000 ppm DMA for 26 weeks or 0 or 2000 ppm DMA for 53 weeks after initiation with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. No significant difference in the incidence/multiplicity of pulmonary proliferative lesions was observed between the groups treated with NNK alone and NNK plus DMA. These results suggest that DMA has no tumor modifying effect in pulmonary proliferative lesions induced in rasH2 and non-Tg mice.